In nature, many substances including proteins and the like are optically active substances, and it is known that a specific bioactivity is expressed according to the stereostructure thereof. Also compounds containing a nitrogen atom are found in great number in natural products. Among them, many of the compounds containing a nitrogen atom in the five-membered ring skeleton are considered to largely contribute to the expression of molecular function.
Therefore, it can be said that establishing a stereoselective synthetic method of a nitrogen-containing compound is important in a total synthesis of a bioactive substance, which is the object in the field of medicine, agricultural chemical, flavor or the like.
As one of the useful processes for constructing a nitrogen-containing five-membered ring skeleton, there is a [3+2] cycloaddition reaction, which has been studied since long time ago. Among them, a cycloaddition reaction using a 1,3-dipole with a high reactivity such as a nitrone has been widely studied, and an example of a catalytic asymmetric reaction using an asymmetric Lewis acid has been reported. Meanwhile, as a [3+2] cycloaddition reaction of an aryl or an acylhydrazone, a cycloaddition reaction of an alkene with an aryl or an acylhydrazone using a protonic acid as a catalyst was reported for the first time in 1970 by Hesse. In addition, it was reported that this reaction proceeds thermally in 1979 by Griggs et al. Since then, several reactions of the same kind have been reported, however, all needs a reaction under a condition with a strong acid or under a thermal condition, and a reaction under a mild condition with the use of a Lewis acid was not known in the past.
Meanwhile, the inventors of this application have reported, until now, various catalytic asymmetric synthesis reactions of a nitrogen-containing compound including the asymmetric Mannich reaction, the aza Diels-Alder reaction, the asymmetric Strecker reation and the like with the use of a chiral zirconium catalyst. Also, at this late date, they have found that intermolecular [3+2] cycloaddition reaction of a hydrazone takes place even under a mild condition with a high yield and a high diastereoselectivity by using a catalytic amount of 10 mol % of zirconium triflate, which has been reported.
However, the fact is that an easy process in which an intramolecular asymmetric cycloaddition reaction of a hydrazone is carried out under a mild condition was not realized. An intramolecular [3+2] asymmetric cycloaddition reaction can not only efficiently construct a polycyclic structure, but also derive a cyclic 1,3-diamine by cleaving the N—N bond of the product, therefore, it can be said that its usability is high.
The invention of this application has been conducted in view of the above-mentioned circumstances, and aims at overcoming the limits of the prior art and providing a process for carrying out an asymmetric intramolecular [3+2] cycloaddition reaction of a hydrazone under a common mild condition with a high stereoselectivity and yield.